PXD055878
PXD055878 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | The SIRT1 activating compound SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery |
Description | Duchenne muscular dystrophy (DMD) is a rare and devastating genetic disorder, whose management is still a major challenge, despite progress in genetic and pharmacological disease-modifying treatments have been made. Mitochondrial dysfunctions contribute to DMD, however, there are no effective mitochondrial therapies for DMD. SIRT1 is a NAD+-dependent class III histone deacetylase that controls several key processes and whose impairment is involved in determining mitochondrial dysfunction in DMD. In addition to well-known resveratrol, other potent selective activators of SIRT1 exist, with better pharmacokinetics properties. Among these, SRT2104 is the most promising and advanced in clinical studies. Here we unveil the beneficial effects of SRT2104 in flies, mice, and patient-derived myoblasts as different models of DMD, demonstrating an anti-inflammatory, anti-fibrotic, and pro-regenerative action of the drug. We also elucidate, by molecular dynamics simulations, that a conformational selection mechanism is responsible for the activation of SIRT1. Further, the impact of SRT2104 in reshaping muscle proteome and acetylome profiles has been investigated, highlighting the drug as an attractive exercise mimetic for the treatment of DMD. Overall, our data suggest SRT2104 as a possible therapeutic candidate to successfully counteract the progression of the dystrophic phenotype in DMD. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-07_02:54:26.082.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD055878 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Erica Gianazza |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Synapt MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-09-16 01:18:21 | ID requested | |
⏵ 1 | 2025-05-07 02:54:26 | announced |
Publication List
10.1038/s41419-025-07595-z; |
Giovarelli M, Zecchini S, Casati SR, Lociuro L, Gjana O, Mollica L, Pisanu E, Mbissam HD, Cappellari O, De Santis C, Arcari A, Bigot A, Clerici G, Catalani E, Del Quondam S, Andolfo A, Braccia C, Cattaneo MG, Banfi C, Brunetti D, Mocciaro E, De Luca A, Clementi E, Cervia D, Perrotta C, De Palma C, The SIRT1 activator SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery. Cell Death Dis, 16(1):259(2025) [pubmed] |
10.6019/PXD055878; |
Keyword List
submitter keyword: metabolism,muscular dystrophy, SIRT1, mitochondria |
Contact List
Clara De Palma | |
---|---|
contact affiliation | Dept of Medical Biotechnology and Translational Medicine,University of Milan, Milan |
contact email | clara.depalma@unimi.it |
lab head | |
Erica Gianazza | |
contact affiliation | Centro Cardiologico Monzino |
contact email | erica.gianazza@cardiologicomonzino.it |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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